Synthesis and properties of pyridine containing drugs and heterocycles

Chapter 1 provides an overview on the chemistry of pyridines and aminopyridines, their biological activities and their synthesis using Bohlmann-Rahtz, Hantzsch and Chichibabin methodology. It discusses the application of modern alternative reaction platforms, such as microwave-assisted synthesis and flow chemistry, of relevance to the synthesis and reactions of pyridine derivatrives. Chapter 2 discusses Lewis acid catalysis in the Bohlmann-Rahtz pyridine synthesis and describes new one-pot, two- and three-component methodologies that have been developed for the synthesis of natural products containing the pyridine motif. These methods have been compared and contrasted and applied to the use of tetranuclear coordination clusters as Lewis acid mixed metal catalysts for Bohlmann-Rahtz cyclodehydration and pyridine synthesis. Chapter 3 discusses the use of the Bohlman–Rahtz pyridine synthesis for the preparation of a range of fused heterocycles containing the pyridine moiety in high yield, including 1,3,7-trimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, 1,3-dimethyl-7-phenylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, 1,7-dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)dione and 1-methyl-7-phenylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione. Chapter 4 describes new substrate scope for the Bohlmann-Rahtz pyridine synthesis by incorporating an amino group at the 2-position of the products. The synthesis of a range of 2,3,6-trisubstituted and 2,3,4,6-tetrasubstituted pyridines was accomplished with total regiocontrol using this new method under microwave-assisted conditions. Chapter 5 describes a new microwave-assisted method for the synthesis of poly-deuterated pyridines. The microwave mediated deuteration of aminopyridine derivatives both with and without the presence of DCl has been studied. The regioselectivity and yields for these processes were compared. Following discovery of a new method for single cycle H/D exchange at multiple positions, high yield and high levels of deuterium incorporation have been found for a range of substrates.